Vinicio Granados Soto - Cannabidiol reduces neuropathic pain and cognitive impairments through activation of spinal PPARγ

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14 de marzo 2025

Te invitamos a leer el artículo: "Cannabidiol reduces neuropathic pain and cognitive impairments through activation of spinal PPARγ",  realizado por el Dr. Vinicio Granados Soto, investigador del Deaprtamento de Farmacobiología en la Sede Sur del Cinvestav.

Autores: Ana Mara Islas Espinoza, Itzel I. Ramos Rodríguez, María J. Escoto Rosales, Juan M. Pizaña Encarnación, Diana K. Morales Galindo, Nadia L. Caram Salas, Myrna Déciga Campos, Erick J. Rodríguez Palma, Vinicio Granados Soto.

Abstrac: The purpose of this study was to evaluate the participation of spinal peroxisome proliferator-activated receptor gamma (PPARy) in the antiallodynic effect of cannabidiol, the expression of PPARy in sites relevant to the spinal nociceptive processing, and the effect of this cannabinoid on cognitive deficits induced by neuropathic pain in female mice. Either acute or repeated treatment with cannabidiol reduced tactile allodynia and spontaneous pain (flinching) in female neuropathic mice. Pioglitazone partially reduced tactile allodynia, and this effect was fully blocked by the PPARy antagonist GW9662. Likewise, intrathecal injection of cannabidiol reduced tactile allodynia, while PPARy antagonist GW9662 or 5-HT1A receptor antagonist WAY-100635, but not the PPARy antagonist GW6479, partially prevented this effect. GW9662 and WAY-100635 administrated per se did not modify tactile allodynia in neuropathic female mice. Co-administration of GW9662 and WAY100635 fully prevented the antiallodynic effect of cannabidiol in mice. Nerve injury up-regulated PPARy expression at the spinal cord and dorsal root ganglia, while cannabidiol further enhanced nerve injury-induced up-regulation of PPARy expression in both tissues. Repeated intrathecal injection of cannabidiol reduced tactile allodynia and several pain makers (ERK, p-ERK, p38MAPK and p-p38MAPK). In addition, this treatment restored nerve injury-induced interleukin-10 down-regulation and increased PPARy expression at the spinal cord. Repeated treatment with cannabidiol also improved nerve injury-induced cognitive impairment in mice. These results provide compelling evidence for the involvement of PPARy in the antiallodynic effect of cannabidiol in mice and highlight its multifaceted therapeutic potential in neuropathic pain management and its comorbidities.

Keywords: Cannabidiol; Cognitive impairment; Neuropathic pain; Mechanism of action; PPARy.